Predictors of mortality and of healthy survival in a large community-based prospective cohort of aging adults with Down syndrome

项目摘要 患有唐氏综合症的成年人比以往任何时候都活得更长，但他们的预期寿命仍然比中国短 普通民众。最常见的死亡原因是呼吸衰竭、痴呆症和 心血管疾病。虽然已经确定了最普遍的死亡原因，但可以修改 死亡率的预测因素仍是未知的。此外，对心血管危险因素进行更全面的评估 他们对死亡率的具体预测价值将帮助我们更好地了解他们的心血管风险概况。 最后，定义一组“健康的幸存者”使我们能够采取“积极生物学”的方法，并确定 老龄化的预测指标没有这个人口正在经历的许多疾病。更好地理解 不可更改和可更改的风险因素(如健康行为)对于进一步抗击早期死亡至关重要 通过制定与生活方式有关的预防计划、早期发现、筛查和诊断战略，以及 充分分配卫生保健资源。 我们建议利用我们的经验和专业知识，以人口为基础， 健康老龄化和智能障碍(HA-ID)纵向队列研究对 唐氏综合征老年患者死亡率和“健康幸存者”预测因素的理解。房委会- ID数据集包括≥50年的1050名智力残疾(ID)的老年成年人，其中包括n=149名成年人 患有唐氏综合症。HA-ID数据集包括一组广泛的基线健康结果，主要 通过临床和面对面评估收集的信息，包括健康行为等可修改的风险因素。 此外，发病率和死亡率是在基线后3年和5年纵向收集的，而10 一年的后续数据收集目前正在完成。我们的长期目标是改善老年人的健康老龄化 确定可改变的危险因素作为与生活方式相关的预防目标的唐氏综合症成人 策略和早期发现和诊断策略。因此，这项研究的拟议目标是： 目标1：描述以社区为基础的唐氏综合症老年患者样本的死亡率和存活率 并与没有唐氏综合症的ID老年成年人的匹配样本进行对比。 目标2：确定可修改和不可修改的死亡率预测因素(包括全面的心血管疾病 在HA-ID研究中，以社区为基础的唐氏综合症老年成年人样本中的风险概况)。 目的3：确定唐氏综合征老年患者“健康幸存者”的特征。 该项目将确定与生活方式相关的战略目标，以支持唐氏综合症成年人的健康老龄化 为早期发现和诊断策略提供了一个有效的方法。这些见解将为分配提供方向 卫生保健资源，通报关于关键卫生措施的纵向研究，以供考虑和启发 唐氏综合征老年患者健康实验研究的机制问题。这些 结果符合美国国立卫生研究院提出的雄心壮志，包括2021年唐氏综合症研究计划。

Project Summary Adults with Down syndrome live longer than ever before, however their life expectancy is still shorter than in the general population. The most common causes of death are respiratory failure, dementia and cardiovascular disease. Although the most prevalent causes of mortality have been identified, modifiable predictors of mortality are still unknown. Additionally, a more inclusive evaluation of cardiovascular risk factors and their specific predictive value for mortality will help us better understand their cardiovascular risk profile. Lastly, defining a group of “healthy survivors” allows us to take a ‘positive biology’ approach and determine the predictors for aging without many of the diseases this population is experiencing. A better understanding of non-modifiable and modifiable risk factors (such as health behaviors) is critical to further combat early mortality by developing lifestyle-related prevention programs, early detection, screening and diagnosing strategies, and adequate allocation of health care resources. We propose to leverage our experience and expertise with the population-based, prospective, longitudinal cohort study Healthy Aging and Intellectual Disability (HA-ID) to uniquely contribute to the understanding of predictors for mortality and “healthy survivors” in aging adults with Down syndrome. The HA- ID dataset includes n=1050 aging adults with intellectual disabilities (ID) of ≥50 years including n=149 adults with Down syndrome. The HA-ID dataset includes an extensive set of baseline health outcomes mostly collected through clinical and in-person evaluation, including modifiable risk factors such as health behaviors. Additionally, morbidity and mortality have been collected longitudinally 3 and 5 years after baseline, and the 10 year follow up data collection is currently being completed. Our long-term goal is to improve healthy aging for adults with Down syndrome by identifying modifiable risk factors as targets for lifestyle-related prevention strategies and early detection and diagnosis strategies. Therefore, the proposed aims of this study are: Aim 1: Describe causes of mortality and survival rates in a community-based sample of aging adults with Down syndrome and contrast with a matched sample of aging adults with ID without Down syndrome. Aim 2: Identify modifiable and non-modifiable predictors of mortality (including a comprehensive cardiovascular risk profile) in a community-based sample of aging adults with Down syndrome in the HA-ID study. Aim 3: Identify the characteristics of ‘healthy survivors’ in aging adults with Down syndrome. This project will identify targets for lifestyle-related strategies to support healthy aging in adults with Down syndrome and for early detection and diagnosis strategies. These insights will provide directions for allocation of health care resources, inform longitudinal studies on critical health measures to consider, and inspire mechanistic questions for experimental studies on health in aging adults with Down syndrome. These outcomes are in line with the ambitions stated in the NIH INCLUDE Down Syndrome Research Plan 2021.